Intrafamilial spread of HBV infection was evaluated in 85 Italian family groups. Secondary infected cases were observed in 43% of these families, of which 73% showed clusters of HBs positive members, with a prevalence among the family members (children-siblings) of the mother/wife index cases, and no strict relation to their "e" system. The presence of the delta agent in the index case was correlated to a higher percentage of secondary HBs-positive cases, but the intrafamilial spread of delta agent was a rare event. A similar higher incidence of HBV markers was observed among the relatives of the index cases positive for auto-antibodies. The evidence presented suggests the importance of genetic factors in the acquisition and clearance of HBV and delta infections.